Oral Immunology - 0517 - L3 4

  1. Origin of immune cells
    • Bone marrow (BM) - pluripotent hematopoietic stem cell (PHSC) -> BM - common lymphoid progenitor (CLP), common myeloid progenitor (CMP)
    • BM - CLP -> blood - B, T, NK cells, ILC (innate lymphoid cell), immature dendritic cell
    • Blood - B/T/NK/ILC cell -> lymph node - B/T/NK/ILC cell -> effector cells - plasma cell/activated T/NK/ILC cell
    • Blood - immature dendritic cell -> lymph node - mature dendritic cell
    • Blood - immature dendritic cell -> tissue - immature dendritic cell -> lymph node - mature dendritic cell
    • BM - CMP -> BM - grannulocyte/macrophage progenitor -> blood - granulocytes or polymorphonuclear leukocytes (PMN): mostly neutrophil, also include eosinophil, basophil, unknown precursor of mast cell, monocyte
    • Blood - unknown precursor of mast cell -> tissue - mast cell
    • Blood - monocyte -> tissue - macrophage
    • BM - CMP -> BM - megakaryocyte/erythrocyte progenitor -> BM - megakaryocyte, erythroblast
    • BM - megakaryocyte -> blood - platelet
    • BM - erythroblast -> blood - erythrocyte
  2. Macrophage
    • Phagocytosis and activation of bactericidal mechanisms
    • Antigen presentation
  3. Dendritic cell
    • Antigen uptake in peripheral sites when immature
    • When mature, Antigen presentation and activate naive T cells in lymphoid organs (after migrate to regional lymph node via lymphatic vessels; can also transfer some Ag to resident dendritic cells)
  4. ________ are immature DCs that take up Ag in the skin, migrate to LNs to present foreign Ag to T cells
    Langerhans cells
  5. Neutrophil
    Phagocytosis and activation of bactericidal mechanisms
  6. Eosinophil
    Kill Ab-coated parasites
  7. Basophil
    Promotion of allergic responses and anti-parasitic immunity
  8. Mast cell
    Release granules w/ histamine and active agents
  9. NK cell
    • Release lytic granules that kill some virus-infected cells
    • Lack Ag-specific receptors , but can detect and kill: herpes virus-infected cells, some tumor cells
  10. Majority of lymphocytes are ______.
    T and B cells
  11. Resting lymphocytes have _________ and __________.
    • small nucleus w/ condensed chromatin
    • relative absence of cytoplasm
  12. Activated lymphocytes
    • larger cytoplasm
    • effector B cell secretes Ig (plasma cell) but has no Ig on surface
  13. Main types of antigen-presenting cells (APCs)
    • Dendritic cell (mature; interdigitating cells; most potent in activating naive T cells)
    • Macrophage
    • B cell
  14. CD4 T cells
    • Helper T cells
    • Recognize complex of antigenic peptide with MHC II and activate B cells
  15. CD8 T cells
    • Cytotoxic T cells
    • Recognize complex of viral peptide w/ MHC I and kill infected cell
  16. Clonal Selection Theory (1950s, by Jerne & Burnet and Talmage) is the Central principle of _______:
    Specificity of immune response resides in ability of its
    components (_________) to __________ and respond to them, in order to eliminate them.
    Failure of the above selection leads to _______, while success of the selection ensures _______.
    • Adaptive Immunity
    • Ag-specific T & B cells
    • recognize particular foreign molecules (antigens)
    • autoimmunity
    • tolerance to self
  17. Colonal Selection
    • Common progenitor -> large number of lymphoid cells w/ different specificity
    • Remove potentially self-reactive immature lymphoid cells by colonal deletion
    • Result in pool of mature naive lymphocytes
    • Proliferation and differentiation of activated Ag-specific lymphocytes to form a colon of effector cells
    • Effector cells eliminate Ag
  18. Hypothetical ways for immune system to detect problems
    • PAMP - pathogen-associated molecular pattern detection (Janeway)
    • DAMP - danger-associated molecular pattern detection (Matzinger); mainly for non-infectious inflammatory responses; nuclear or cytosolic proteins, released tumor DNA
  19. evidence for PAMP
    Common molecular motiffs are found on a number pathogens
  20. evidence for PAMP
    leaked components of damaged and dying or dead cells
  21. TLR
    • Toll-like receptors
    • found on macrophage, dendritic cells, etc.
    • can recognize both PAMP and DAMP
    • Part of innate immune system
  22. TLR-1:TLR-2
    • PAMPs and DAMPs
    • plus MD-2 and CD14 - LPS (G-) and lipoteichoic acids (G+)
    • Flagella
    • SS RNA (viruses)
    • DNA w/ CpG (bacteria and herpes viruses)
    • human only; unknown
  23. CD markers
    • All T cells: CD3+
    • Th - CD4+ alpha:beta
    • Tc - CD8+ alpha:beta
    • minority - CD4-,CD8-,gamma:delta
    • All B cells: Ig+ (terminal B, aka plasma cells don't have Ig on surface)
    • Subpopulation of B cells from fetal liver: CD5+
    • NK cells: no specific Ag recognition marker; Ig-, CD3-; CD16+
  24. Innate antimicrobial mechanisms
    • Rapid, non-specific
    • Prevention of colonization
    • Removal of colonized pathgens
  25. Response to an initial infection
    • Body barrier
    • Innate immunity: 0-4hrs. Preformed nonspecific and broadly specific effectors
    • Early induced innate response: 4-96hrs. Recruit effector. Activation of effector cells and inflammation. TLR recognize PAMPs
    • Adaptive immune response: >96hrs. Transport antigen to lymphoid organs; recognized by naive T & B cells; colonal expansions and differentiation to effector cells.
  26. Components of Innate Immunity
    • Anatomical barriers
    • – Mechanical factors (skin, epithelia, etc.)
    • – Chemical factors
    • – Biological factors
    • Humoral components
    • – Complement
    • – Coagulation system
    • – Cytokines (TNF-a, IL-1, Interferons, etc.)
    • Cellular components
    • – Circulating phagocytic cells (neutrophils, macrophages, NK cells)
    • – Eosinophils
    • – Intraepithelial lymphocytes
  27. Routes of pathogenic infection
    • Airway
    • Gastrointestinal tract
    • Reproductive tract
    • Oral mucosa
  28. Stages of response to an infection
    • Adherence to epithelium - esp. in lung
    • Penetration of epithelium, local infection - wound healing; antimicrobial agents action
    • Local infection of tissue - dendritic cell migrates; initiate adaptive immunity
    • Adaptive immunity - Ab, T-dependent macrophage, Tc
  29. Barrier function in innate immunity
    • Mechanical: tight junction btwn epi cells; flow of air/fluid; movement of mucus by cilia.
    • Chemical
    • Microbiological: normal microbiota; commensal
  30. Chemical barrier in innate immunity
    • Skin - fatty acids; beta-defensins, lamellar bodies, cathelicidin
    • Gut - low pH; enzymes (pepsin); alpha-defensins (cryptdins), RegIII (lecticidins), cathelicidin
    • Lungs - pulmonary surfactant; alpha-defensins, cathelicidin
    • Eyes/nose/oral cavity - enzymes in tears and saliva (lysozyme); histatins, beta-defensins
  31. Antimicrobial mechanisms of phagocytes
    • Acidification - pH 3.5-4
    • Toxic oxygen-derived products - superoxide, etc
    • Toxic nitrogen oxides - NO
    • Antimicrobial peptides - both macrophages and neutrophil produce cathelicidin, in addition to ...
    • Enzymes - lysozyme vs cell wall of some G(+); acid hydrolases break down ingested microbes
  32. Antimicrobial enzymes:
    • tears, saliva, paneth cells
    • Lysozyme: cleaves β(1-4) linkage in peptidoglycan of bacterial cell wall; G+ >> G-; exposes lipid bilayer cell membrane
    • Secretary phospholipase A2: hydrolyzes phospholipid
  33. Antimicrobial Peptides
    • Short, generally cationic, broad-spectrum antimicrobial proteins
    • Defensins, Cathelicidin, Histatins
    • Found in myeloid cells
    • – Neutrophils, alveolar macrophages
    • Found at mucosal surfaces
    • – Saliva, trachea, small intestine, female reproductive tract
  34. alpha- and beta-Defensins
    • Basic, Cysteine-Rich Antimicrobial Peptides
    • 6 cysteines in defined consensus sequence w/ 3 disulfide bonds
    • broad-spectrum antibiotic - bacteria, fungi, enveloped viruses, mycobacterium
  35. Cathelicidin (LL-37)
    • Broad-spectrum antimicrobial peptide found in both neutrophils and epithelial cells
    • Protected from its action by cathelin, has to be cleaved to release LL-37 to make it active
  36. Histatins
    • Found only in saliva
    • Antifungal - Highly active against candida
  37. Defensins, cathelicidins, and histatins are activated by ______ to release _________.
    • proteolysis
    • an amphipathic antimicrobial peptide
  38. Response of cells to LPS
    • CD14
    • - GPI-linked; no cytoplasmic domain
    • - Membrane bound and soluble forms
    • LPS-binding protein (LBP)
    • - Found in serum
    • Toll-like receptors
    • - hTLR4 associates with LPS, CD14 and MD-2
    • Binding of LPS to TLR4 and CD14 activates a kinase cascade
    • Degradation of I-kB (inhibitor) leads to activation of NF-kB
    • Active NF-kB translocates into the nucleus and induces transcription of host defense genes
  39. Cellular locations of mammalian Toll-like receptors
    • Plasma membrane: 1:2 (lipopeptide), 2:6 (lipopeptide), 4 (LPS), 5 (flagella)
    • ER: 7 (ssRNA), 9 (CpG DNA), 3 (dsRNA)
  40. Mammalian TLRs interact with different TIR-domain adaptor molecules to activate downstream signaling pathways, while most of them converge at ______.
  41. Induction of innate immunity by binding of LPS to ___:
    • TLR4
    • GPI-linked CD14 bind to LPB-LPS, docks to TLR4, then MyD88 and TRAF6, then IKK, eventually NF-kB is activated, turns on production of cytokines, chemokines, for receptor response
  42. Induction of innate immunity by binding to proteoglycan:
    • either TLR2 or cytosolic protein NOD2 (Muramyl dipeptide)
    • eventually activates transcription factor NF-kB
    • activate transcription of gene for immune responses
Card Set
Oral Immunology - 0517 - L3 4
Oral Immunology - 0517 - L3,4